Sepsis and septic shock represent the most common cause of death in ICU patients. It is very likely that much of the morbidity and mortality associated with sepsis results from endogenous mediators released by host defense systems in response to bacterial invasion. One such host defense system includes the endogenous cytokines. Tumor necrosis factor, one such cytokine, has been speculated to play an important role in sepsis induced tissue injury and organ dysfunction. We have evaluated the effects of tumor necrosis factor on cardiopulmonary function in a chronically tracheotomized canine model. Purpose bred beagles were instrumented under local anesthesia with femoral and pulmonary arterial catheters. Measurements of pulmonary gas exchange and systemic cardiopulmonary hemodynamics, as well as bronchoalveolar lavage were performed seven days before, on the day of, and 1, 3, 6, 8 and 21 days after tumor necrosis factor infusion. Tumor necrosis factor produced significant abnormalities of systemic and pulmonary hemodynamics, pulmonary gas exchange, and in alveolar cell analysis and protein accumulation. Tumor necrosis factor appears capable of producing many of the abnormalities of cardiopulmonary function associated with bacterial sepsis. Therapies directed toward modifying tissue reactions to tumor necrosis factor during systemic infection may be useful in preventing tissue injury during bacterial sepsis.